Late Growth and Changes in Body Composition Influence Odds of Developing Retinopathy of Prematurity among Preterm Infants.

BACKGROUND: While postnatal growth in the first month of life is known to impact retinopathy of prematurity (ROP) risk, the impact of growth later in hospitalization, during critical times of retinal vascularization, remains unknown. The purpose of this study was to assess if postnatal growth and body composition during the second half of neonatal intensive care unit hospitalization were associated with severity of retinopathy of prematurity in very low birth weight preterm infants. METHODS: Prospective observational pilot study of 83 infants born <32 weeks gestation and <1500 g, conducted at a Level IV neonatal intensive care unit. Body composition was measured during the second half of hospitalization. Infants were evaluated for retinopathy of prematurity. Logistic regression was performed. RESULTS: Greater gains in fat mass, fat-free mass, and percent body fat from 32 to 37 weeks postmenstrual age and higher % body fat at term postmenstrual age were associated with decreased odds of ≥stage 2 retinopathy of prematurity (p < 0.05). CONCLUSIONS: Improved growth later in neonatal intensive care unit hospitalization and increased adiposity at term may reduce odds of severe retinopathy of prematurity.

Iron is prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs.

BACKGROUND: Critically ill preterm and term neonates are at high risk for negative iron balance due to phlebotomy that occurs with frequent laboratory monitoring, and the high iron demand of rapid growth. Understanding the prioritization of iron between red blood cells (RBCs) and brain is important given iron's role in neurodevelopment. METHODS: Ten neonatal twin lamb pairs (n = 20) underwent regular phlebotomy for 11 d. Lambs were randomized to receive no iron or i.v. daily iron supplementation from 1 to 5 mg/kg. Serum hemoglobin concentration and reticulocyte count were assayed, iron balance calculated, and iron content of RBCs, liver, brain, muscle, and heart measured at autopsy. RESULTS: Among phlebotomized lambs: (i) liver iron concentration was directly related to net iron balance (r = 0.87; P < 0.001) and (ii) brain iron concentration was reduced as a function of net iron balance (r = 0.63) only after liver iron was depleted. In animals with negative iron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs (r = -0.70; P < 0.01) and as a function of reticulocyte count (r = -0.63; P < 0.05). CONCLUSION: Phlebotomy-induced negative iron balance limits iron availability to the developing brain.

Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder.

An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (lncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including lncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. These deletions define a distant cis-regulatory region that harbors, besides lncRNA genes, also a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. We suggest that lung-transcribed 16q24.1 lncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of lncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development.

Developmental changes in the responses of preterm infants to a painful stressor.

The purpose of this investigation was to examine longitudinally gestational age and developmental differences in preterm infants' self-regulatory abilities in response to a painful stressor, as well as associations between behavioral and cardiovascular responses. Participants included 49 healthy premature infants. Behavioral and cardiovascular responses to a heel stick blood draw were compared between infants of 28-31 and 32-34 weeks' gestation age at birth. Both gestational age groups displayed behavioral and cardiovascular indications of stress in response to the blood draw. However, both shortly after birth and several weeks later, infants born at younger gestational ages (28-31 weeks) were more physiologically reactive. Evidence that the behavioral stress responses of 28-31 weeks' gestation age group preterm infants do not reflect their physiological responses suggests that evaluation of preterm infants' experiences and risk require assessments of both physiology and behavior. The greater stress vulnerability of the 28-31 weeks' gestation group relative to the 32-34 weeks' gestation group and the implications of this for subsequent development are discussed.

Effects of prenatal betamethasone exposure on regulation of stress physiology in healthy premature infants.

The objective of this study was to examine the effects of prenatal exposure to betamethasone, a corticosteroid, on postnatal stress regulation, particularly activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Effects were assessed by measuring salivary cortisol production at baseline and in response to two potentially stressful events, a heel-stick blood draw and a physical exam, in infants born at 33-34 weeks gestation. Subjects included 9 infants with antenatal betamethasone treatment (2 doses of 12 mg of betamethasone administered intramuscularly to the mother twelve hours apart) and 9 infants without such treatment. Testing took place 3-6 days after delivery. Measures of behavioral distress confirmed that both events were stressful to these premature infants. Infants with betamethasone exposure, however, failed to exhibit increases in cortisol to either stressor. In contrast, infants without betamethasone exposure displayed elevated cortisol to the heel-stick blood draw but not the physical exam. These findings suggest that antenatal corticosteroids suppress infants' HPA response to a stressor typically encountered in a neonatal intensive care situation.